Clearing Out 'Old Cells' Might Make for Healthier Old Age

WEDNESDAY Nov. 2, 2011 -- Sweeping away the body's old cells may help delay age-related health woes and give more pep to old age, a new study in mice suggests.

In a study published online Nov. 2 in Nature, Mayo Clinic scientists came up with a way to eliminate so-called "senescent" cells -- aging cells that stop functioning properly but still stick around the body, damaging healthy tissues, explained study author Dr. Jan van Deursen, a professor of pediatrics, molecular biology and biochemistry at the Mayo Clinic in Rochester, Minn.

"This research has identified a cell class that makes you old and makes you have age-related declines. We can now start to think about how you can get rid of them," he said.

According to van Deursen, "how organisms and people age is not really well understood, particularly not at a cell and molecular level. There are many theories about how we age and one of the theories that we investigated was that as we age, senescent cells start to accumulate and produce and secrete proteins and other factors that basically make the healthy neighboring cells that surround them less functional."

After "deleting" senescent cells in mice genetically engineered to age quickly, tissues remained healthier and performed better, van Deursen's team found.

Senescent cells are limited in number, making only up to 15 percent of cells in an elderly person, for example. To eliminate them in the mice, the researchers focused a tracer on a protein called p16, explained co-author Dr. James Kirkland, director of the Mayo Clinic's Robert and Arlene Kogod Center on Aging.

P16 stops cells from dividing and can trigger a series of steps that causes cellular senescence, Kirkland said.

"In healthy young cells the p16 gene is not expressed," van Deursen added. "Later on, as we age, it becomes higher in our tissues."

The scientists used p16 to activate a type of "suicide gene" within senescent cells. The protein made by this gene will kill senescent cells (without harming other normal cells) after a drug specifically designed to activate it is administered, said van Deursen.

Two sets of prematurely aged mice were involved. In one set, the researchers cleared senescent cells for the whole 15 months of the mice's typical lifespan. In another set of mice, they waited until age-related problems were well underway and then cleared the senescent cells away for a few months, said Kirkland.

The result: Lifelong destruction of a mouse's senescent cells kept age-related problems at bay, including cataracts and loss of muscle mass and strength. But the study also suggested that removing senescent cells later in life could slow down these age-related health problems.

What's more, said Kirkland, improved behavior was noted -- the activity level of the mice was considerably higher.

Still, the research is early and has not yet moved into experiments in humans. "It's a proof of principle study. Now we know we can safely remove these cells in an animal model without causing any detectable harm," said van Deursen.

Dr. Gary Kennedy, director of the Division of Geriatric Psychiatry at Montefiore Medical Center in the Bronx, and an expert in aging, said the work was exciting.

"When they blocked the senescent cell process in mice prone to premature aging, they blocked the development of spinal arthritis, the loss of muscle, thinning of skin -- they were all reversed. Mice that should have looked prematurely aged were essentially normal," Kennedy noted. But he stressed that the research needs to be replicated in other species as well before the public gets excited about its medical promise.

"I thought it was a very interesting paper. I was actually surprised by the data -- no one else has been able to do this," added Dr. Julian Sage, an associate professor of pediatrics and genetics at Stanford University. He said the "genetic trick" they used to eliminate the cell was intriguing, and he was equally interested in the finding that when you clear senescent cells that damage is curtailed.

Sage said the next big question is how to determine when and how many senescent cells to remove to have a positive health impact.

"The tricky part in people will be how many senescent cells you can eliminate without killing the person, but to have an effect," Sage believes.

Another expert agreed the findings were intriguing.

"It's an elegant study and a most important discovery," said Dr. Nir Barzilai, professor of medicine and genetics and director of the Institute for Aging Research at Albert Einstein College of Medicine, in New York City. He said it's been suggested that senescence is a protective mechanism, against cancer, for example. However, "this paper really suggests that senescence is not good or neutral, but in fact, if cleared, can be associated with less aging," he said.

The findings invite countless avenues for future research, said the authors.

"If you attack the fundamental aging process, can you attack age-related illnesses as a whole?" Kirkland wondered. "Can you delay cancer, dementias, atherosclerosis, diabetes, obesity and its complications as a group?"